19-55018667-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001083899.2(GP6):c.709G>A(p.Glu237Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 1,598,796 control chromosomes in the GnomAD database, including 529,133 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 46051 hom., cov: 33)

Exomes 𝑓: 0.82 ( 483082 hom. )

Consequence

GP6
NM_001083899.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.136

Variant links:

Genes affected

GP6 (HGNC:14388): (glycoprotein VI platelet) This gene encodes a platelet membrane glycoprotein of the immunoglobulin superfamily. The encoded protein is a receptor for collagen and plays a critical role in collagen-induced platelet aggregation and thrombus formation. The encoded protein forms a complex with the Fc receptor gamma-chain that initiates the platelet activation signaling cascade upon collagen binding. Mutations in this gene are a cause of platelet-type bleeding disorder-11 (BDPLT11). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

GP6 links:

GP6-AS1 (HGNC:55305): (GP6 antisense RNA 1)

GP6-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.058281E-7).

BP6

Variant 19-55018667-C-T is Benign according to our data. Variant chr19-55018667-C-T is described in ClinVar as [Benign]. Clinvar id is 257423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-55018667-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GP6	NM_001083899.2 link	c.709G>A	p.Glu237Lys	missense_variant	Exon 6 of 8	ENST00000310373.7	NP_001077368.2	Q9HCN6-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GP6	ENST00000310373.7 link	c.709G>A	p.Glu237Lys	missense_variant	Exon 6 of 8	1	NM_001083899.2	ENSP00000308782.3		Q9HCN6-3
GP6	ENST00000417454.5 link	c.709G>A	p.Glu237Lys	missense_variant	Exon 6 of 8	1		ENSP00000394922.1		Q9HCN6-1

Frequencies

GnomAD3 genomes

AF:

0.772

AC:

117437

AN:

152052

Hom.:

46044

Cov.:

show subpopulations

Gnomad AFR

AF:

0.623

Gnomad AMI

AF:

0.770

Gnomad AMR

AF:

0.810

Gnomad ASJ

AF:

0.796

Gnomad EAS

AF:

0.822

Gnomad SAS

AF:

0.722

Gnomad FIN

AF:

0.877

Gnomad MID

AF:

0.848

Gnomad NFE

AF:

0.836

Gnomad OTH

AF:

0.804

GnomAD3 exomes

AF:

0.807

AC:

201296

AN:

249554

Hom.:

81857

AF XY:

0.805

AC XY:

108994

AN XY:

135398

show subpopulations

Gnomad AFR exome

AF:

0.609

Gnomad AMR exome

AF:

0.837

Gnomad ASJ exome

AF:

0.800

Gnomad EAS exome

AF:

0.834

Gnomad SAS exome

AF:

0.728

Gnomad FIN exome

AF:

0.872

Gnomad NFE exome

AF:

0.829

Gnomad OTH exome

AF:

0.815

GnomAD4 exome

AF:

0.816

AC:

1180211

AN:

1446626

Hom.:

483082

Cov.:

AF XY:

0.815

AC XY:

587177

AN XY:

720582

show subpopulations

Gnomad4 AFR exome

AF:

0.611

Gnomad4 AMR exome

AF:

0.833

Gnomad4 ASJ exome

AF:

0.798

Gnomad4 EAS exome

AF:

0.806

Gnomad4 SAS exome

AF:

0.732

Gnomad4 FIN exome

AF:

0.872

Gnomad4 NFE exome

AF:

0.827

Gnomad4 OTH exome

AF:

0.805

GnomAD4 genome

AF:

0.772

AC:

117487

AN:

152170

Hom.:

46051

Cov.:

AF XY:

0.776

AC XY:

57734

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.623

Gnomad4 AMR

AF:

0.810

Gnomad4 ASJ

AF:

0.796

Gnomad4 EAS

AF:

0.821

Gnomad4 SAS

AF:

0.722

Gnomad4 FIN

AF:

0.877

Gnomad4 NFE

AF:

0.836

Gnomad4 OTH

AF:

0.802

Alfa

AF:

0.795

Hom.:

27038

Bravo

AF:

0.761

TwinsUK

AF:

0.825

AC:

3058

ALSPAC

AF:

0.820

AC:

3162

ESP6500AA

AF:

0.625

AC:

2441

ESP6500EA

AF:

0.833

AC:

6911

ExAC

AF:

0.800

AC:

96713

Asia WGS

AF:

0.750

AC:

2610

AN:

3478

EpiCase

AF:

0.830

EpiControl

AF:

0.832

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Platelet-type bleeding disorder 11

Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.1

DANN

Benign

0.54

DEOGEN2

Benign

0.019

T;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0023

MetaRNN

Benign

9.1e-7

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.4

N;N;.

PrimateAI

Benign

0.33

PROVEAN

Benign

0.58

N;N;N

REVEL

Benign

0.0070

Sift

Benign

0.79

T;T;T

Sift4G

Benign

0.95

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.13

MPC

0.19

ClinPred

0.00050

GERP RS

-1.8

Varity_R

0.028

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over